GEN News Highlights

Genetic Abnormalities Found in Pluripotent Stem Cell Lines

A multinational team of researchers has documented specific genetic abnormalities that occur in human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) lines. The findings highlight the need for frequent genomic monitoring of pluripotent stem cells to assure their stability and clinical safety.

The study titled “Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture” is published in the January 7 issue of Cell Stem Cell. The research was led by stem cell scientists at the University of California, San Diego (UCSD) School of Medicine and Scripps Research Institute.

“We found that human pluripotent cells had higher frequencies of genomic aberrations than other cell types,” says Louise Laurent, M.D., Ph.D., assistant professor in the UCSD department of reproductive medicine and first author on the study. “Most strikingly, we observed a higher frequency of genomic duplications in hESCs and deletions in iPSCs when compared to nonpluripotent samples.”

The team performed high-resolution SNP analysis on 186 pluripotent and 119 nonpluripotent samples. They found variations enriched in specific genomic regions. The distribution of these variations differed between hESCs and IPSCs, characterized by large numbers of duplications found in a few hESC samples and moderate numbers of deletions distributed across many IPSC samples. For IPSCs the reprogramming process was associated with deletions of tumor-suppressor genes, whereas time in culture was associated with duplications of oncogenic genes.

“We were surprised to see profound genetic changes occurring in some cultures over very short periods of time, such as during the process of reprogramming somatic cells into iPSCs and during differentiation of the cells in culture,” Dr. Laurent remarks. “We don’t know yet what effects, if any, these genetic abnormalities will have on the outcome of basic research studies or clinical applications, and we need to find out.”

Senior author Jeanne F. Loring, Ph.D., professor and director of the Center for Regenerative Medicine at the Scripps Research Institute, adds, “Since genetic aberrations are often associated with cancers, it is vital that cell lines destined for clinical use are free from cancer-associated genomic alterations.”

Dr. Loring concludes, “The results of the study illustrate the need for frequent genomic monitoring of pluripotent stem cell cultures. SNP analysis has not been a part of routine monitoring of hESC and iPSC cultures, but our results suggest that perhaps it should be.”

Jobs

GEN Jobs powered by HireLifeScience.com connects you directly to employers in pharma, biotech, and the life sciences. View 40 to 50 fresh job postings daily or search for employment opportunities including those in R&D, clinical research, QA/QC, biomanufacturing, and regulatory affairs.

If you have any questions about your subscription, click
hereto email us or call at (914) 740-2189.

You may also be interested in subscribing to the GEN magazine, an indispensable
resource for everyone involved in the business of translating discoveries at the
bench into solutions that fight disease and improve health, agriculture, and the
environment. Subscribe
today to see why over 60,000 biotech professionals read GEN to
keep current in the areas of genomics, proteomics, drug discovery, biomarker discovery,
bioprocessing, molecular diagnostics, collaborations, biotech business trends, and
more.